ArticleBiochemistry2016
Membrane Interactions, Ligand-Dependent Dynamics, and Stability of Cytochrome P4503A4 in Lipid Nanodiscs.
Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Lipid Dependence of CYP3A4 Activity in Nanodiscs.Biology · 2026Article
- Construction of Well-Defined Yet Adaptable Oligo(Amino Acid) Cavities within an Aromatic Micelle.Journal of the American Chemical Society · 2026Article
- Mass spectrometry footprinting reveals microsomal CYP2A6 structural changes induced by interaction with its reductase flavin mononucleotide domain.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- The Nanodisc System for Investigating Protein-Lipid Interactions.Methods in molecular biology (Clifton, N.J.) · 2026Review
- From closed to open: three dynamic states of membrane-bound cytochrome P450 3A4.Journal of computer-aided molecular design · 2025Article
- Multiresolution molecular dynamics simulations reveal the interplay between conformational variability and functional interactions in membrane-bound cytochrome P450 2B4.Protein science : a publication of the Protein Society · 2024Article
- Dark nanodiscs for evaluating membrane protein thermostability by differential scanning fluorimetry.Biophysical journal · 2024Article
- Direct interaction between the transmembrane helices stabilize cytochrome P450 2B4 and cytochrome b5 redox complex.Biophysical chemistry · 2023Article
- Induced Fit Describes Ligand Binding to Membrane-Associated Cytochrome P450 3A4.Molecular pharmacology · 2023Article
- Nanodisc-embedded cytochrome P450 P3A4 binds diverse ligands by distributing conformational dynamics to its flexible elements.Journal of inorganic biochemistry · 2023Article
- Detergent-Free Isolation of Membrane Proteins and Strategies to Study Them in a Near-Native Membrane Environment.Biomolecules · 2022Review
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Molecular Lego of Human Cytochrome P450: The Key Role of Heme Domain Flexibility for the Activity of the Chimeric Proteins.International journal of molecular sciences · 2022Article
- Structural Dynamics of Cytochrome P450 3A4 in the Presence of Substrates and Cytochrome P450 Reductase.Biochemistry · 2021Article
- Nanodisc reconstitution of flavin mononucleotide binding domain of cytochrome-P450-reductase enables high-resolution NMR probing.Chemical communications (Cambridge, England) · 2021Article
- Nanodiscs: A toolkit for membrane protein science.Protein science : a publication of the Protein Society · 2021Review
- Dynamics and Mechanism of Binding of Androstenedione to Membrane-Associated Aromatase.Biochemistry · 2020Article
- Characterization of the structure and interactions of P450 BM3 using hybrid mass spectrometry approaches.The Journal of biological chemistry · 2020Article
- Dynamics and Location of the Allosteric Midazolam Site in Cytochrome P4503A4 in Lipid Nanodiscs.Biochemistry · 2020Article
- The hydrodynamic motion of Nanodiscs.Chemistry and physics of lipids · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Membrane-bound cytochrome P4503A4 (CYP3A4) is the major source of enzymatic drug metabolism. Although several structural models of CYP3A4 in various ligand complexes are available, none includes a lipid bilayer. Details of the effects of the membrane on protein dynamics and solvation, and access channels for ligands, remain uncertain. H/D exchange mass spectrometry (H/DXMS) with ligand free CYP3A4 containing a deletion of residues 3-12, compared to that of the full length wild type, in lipid nanodiscs afforded 91% sequence coverage. Deuterium exchange was fast in the F- and G-helices, HI loop, and C-terminal loop. In contrast, there is very low exchange in the F'- and G'-helices. The results are consistent with the overall membrane orientation of CYP3A4 suggested by published MD simulations and spectroscopic results, and the solvent accessibility of the F/G loop suggests that it is not deeply membrane-embedded. Addition of ketoconazole results in only modest, but global, changes in solvent accessibility. Interestingly, with ketoconazole bound some peptides become less solvent accessible or dynamic, including the F- and G-helices, but several peptides demonstrate modestly increased accessibility. Differential scanning calorimetry (DSC) of CYP3A4-nanodiscs suggests membrane-induced stabilization compared to that of aggregated CYP3A4 in buffer, and this stabilization is enhanced upon addition of the ligand ketoconazole. This ligand-induced stabilization is accompanied by a very large increase in ΔH for CYP3A4 denaturation in nanodiscs, possibly due to increased CYP3A4-membrane interactions. Together, the results suggest a distinct orientation of CYP3A4 on the lipid membrane, and they highlight likely solvent access channels, which are consistent with several MD simulations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.